Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biologic and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential change in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: 1) CT imaging of L3 prior to and after treatment, and 2) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher loss of SMMi after treatment (-11.1% vs. -6.3%, p = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs. -7.1%, p=0.04). In addition, HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs. 77.9, p=0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM were associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.
Endocrine-related cancer. 2024 Sep 01 [Epub ahead of print]
Neha Venkatesh, Rebecca S Tidwell, Yao Yu, Ana Aparicio, Amado J Zurita, Sumit K Subudhi, Bilal A Siddiqui, Sagar S Mukhida, Justin R Gregg, Paul G Corn, Efstratios Koutroumpakis, Jennifer L McQuade, Daniel E Frigo, Patrick G Pilie, Chad Huff, Christopher J Logothetis, Andrew W Hahn
N Venkatesh, N/A, Baylor College of Medicine, Houston, United States., R Tidwell, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, United States., Y Yu, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, United States., A Aparicio, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., A Zurita, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., S Subudhi, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., B Siddiqui, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., S Mukhida, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., J Gregg, Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, United States., P Corn, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., E Koutroumpakis, Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, United States., J McQuade, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., D Frigo, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., P Pilie, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., C Huff, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, United States., C Logothetis, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States., A Hahn, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.